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      Impact of Growth Hormone Administration on Other Hormonal Axes

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          Growth hormone regulates several other hormonal systems and vice versa. The present review focusses on the effect of GH administration in adults on selected hormonal systems. Growth hormone treatment has been linked to development of central hypothyroidism in hypopituitary children. We now know that GH enhances the extra-thyroidal conversion of T<sub>4</sub> to T<sub>3</sub>. Lowering of T<sub>4</sub> during GH treatment therefore reflects biochemical unmasking of subclinical central hypothyroidism. In normal adults GH administration does not affect the pituitary-gonadal axis. There is, however, evidence to suggest that GH substitution in hypopituitary adults enhances peripheral actions of sex steroids (males) and stimulates gonadal function (females). Both increased, unchanged and reduced basal and ACTH stimulated glucocorticoid levels have been reported during GH treatment. Several groups have recorded reduced levels of cortisol binding globulin with unchanged free cortisol concentrations. Regular assessment of thyroid and glucocorticoid status during GH substitution in GH-deficient patients is recommended.

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          Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study.

          Insulin-like growth factor-I (IGF-I) is a mitogen for prostate epithelial cells. To investigate associations between plasma IGF levels and prostate cancer risk, a nested case-control study within the Physicians' Health Study was conducted on prospectively collected plasma from 152 cases and 152 controls. A strong positive association was observed between IGF-I levels and prostate cancer risk. Men in the highest quartile of IGF-I levels had a relative risk of 4.3 (95 percent confidence interval 1.8 to 10.6) compared with men in the lowest quartile. This association was independent of baseline prostate-specific antigen levels. Identification of plasma IGF-I as a predictor of prostate cancer risk may have implications for risk reduction and treatment.
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            Effects of Growth Hormone Replacement Therapy on IGF-Related Parameters and on the Pituitary-Gonadal Axis in GH-Deficient Males

            It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some of which are similar to the effects of gonadal steroids. However, little is known about the potential effects of GH on gonadal steroids and on dynamic tests of pituitary-gonadal function in adults with GH deficiency. We evaluated the pituitary-gonadal axis in a 4-month double-blind, placebo-controlled GH study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) µg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) µg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) µg/l and ALS levels from 9,182 (5,524) to 16,872 (6,278) µg/l (all p < 0.0001). We found no differences in basal testosterone levels in the 13 patients between the GH and placebo treatment periods (21.9 (5.1) vs. 24.5 (8.1) nmol/l, nonsignificant). Furthermore, no effect of GH on the testicular response to hCG after 72 h was seen compared to placebo (36.2 (6.4) vs. 38.8 (10.3) nmol/l). In addition, no differences existed in basal SHBG, DHT, free testosterone, Δ4-adion and DHEA-S levels. There were no statistically significant differences in maximal FSH and LH response to a GnRH challenge between the GH and the placebo periods (15.7 (5.3) vs. 18.0 (8.8) U/l and 47.0 (26.4) vs. 40.4 (26.5) U/l, respectively). Furthermore, there was no effect on cortisol responses after ACTH between the GH and the placebo periods. However, significantly higher estradiol levels were seen after GH treatment (110 (50) pmol/l) compared to after placebo (89 (34) pmol/l, p = 0.03). Prostate-specific antigen levels decreased after GH treatment compared to after placebo (0.42 (0.54) vs. 0.47 (0.48) µg/l) and this difference almost reached statistical significance (p = 0.059). Inhibin-B levels were significantly lower in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1) the pituitary FSH and LH response to GnRH; (2) basal and hCG-stimulated levels of androgens and SHBG; (3) basal inhibin-B levels; (4) ACTH-stimulated cortisol secretion. By contrast, GH administration had subtle anti-androgenic effects in terms of elevated elevated estradiol levels and decreased prostate-specific antigen levels, although both parameters remained within the normal range. Thus, at the level of blood chemistry the effects of GH administration do not appear to involve major alterations in the pituitary-gonadal axis.

              Author and article information

              Horm Res Paediatr
              Hormone Research in Paediatrics
              S. Karger AG
              November 1999
              17 November 2004
              : 51
              : Suppl 3
              : 121-126
              aMedical Department M (Endocrinology and Diabetes), and bDepartment of Gynaecology and Obstetrics, Aarhus University Hospital, Aarhus; cDepartment of Growth and Reproduction, University Hospital of Copenhagen, Denmark
              53174 Horm Res 1999;51(suppl 3):121–126
              © 1999 S. Karger AG, Basel

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              Page count
              Figures: 3, References: 25, Pages: 6
              Workshop: Adverse Effects in GH Treatment


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